Is BTN2A2 p.Phe365= (c.1095C>T) pathogenic?

BTN2A2 p.Phe365= (c.1095C>T) is classified Likely benign in BTN2A2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-21). Ultra-rare (popmax 0.0154%, sas); Associated with BTN2A2-related disorder.

What condition is associated with BTN2A2 p.Phe365= (c.1095C>T)?

BTN2A2 p.Phe365= (c.1095C>T) is associated with BTN2A2-related disorder (ClinVar).

How common is BTN2A2 p.Phe365= (c.1095C>T) in the general population?

BTN2A2 p.Phe365= (c.1095C>T) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

BTN2A2 p.Phe365=

c.1095C>T · rs776923192 · VCV3039298

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Conditions

BTN2A2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.5	GERP -3.7
Overall
CADD	3.323	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/91,080 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.0018% 29/1,614,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,506
African / African-American	0.00533%	18,762
Remaining individualsnot grpmax-eligible	0.0032%	31,256
Admixed American	0.00167%	60,024
European (non-Finnish)	0.000678%	147,505

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BTN2A2
Protein: p.Phe365=
Coding: c.1095C>T
MANE Select: NM_006995
dbSNP: rs776923192
Type: single nucleotide variant
Location: chr6:26392490 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 1 PDB
Residue 365: the b30.2/spry domain

Full BTN2A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BTN2A2-related disorder

Similar variants

BTN2A2 c.443-8C>G Likely benign same condition
BTN2A2 c.932-3C>T Likely benign same condition
BTN2A2 c.980-88G>C Benign same condition
BTN2A2 p.Ala192Ser Likely benign same condition
BTN2A2 p.Ala336Thr Benign same condition
BTN2A2 p.Asn118= Likely benign same condition
BTN2A2 p.Gly203Ser Benign ⚠ same condition
BTN2A2 p.Leu19= Benign same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/btn2a2-p-phe365 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown